p67phox

p67phox, also known as neutrophil cytosolic factor 2 (NCF2), is a cytosolic regulatory subunit of the phagocyte NADPH oxidase complex. It is expressed mainly in neutrophils and monocytes and functions together with other cytosolic subunits to regulate the production of reactive oxygen species during the respiratory burst.

In resting cells, p67phox forms part of a cytosolic complex with p47phox and p40phox. Upon activation, this complex translocates to the membrane and associates with the membrane-bound flavocytochrome b558 (composed of gp91phox and p22phox). There, the assembled NADPH oxidase transfers electrons from NADPH to molecular oxygen, generating superoxide anion, a key antimicrobial agent. The activity of p67phox is coordinated with the small GTPase Rac2, which is required for full enzyme activation. Structurally, p67phox contains a PB1 domain that mediates interaction with p40phox, as well as regions that interact with Rac and other components, enabling proper assembly and regulation of the oxidase complex.

Genetically, the NCF2 gene encodes p67phox in humans. Mutations in NCF2 can cause autosomal recessive forms of chronic granulomatous disease (CGD), a primary immunodeficiency characterized by impaired production of reactive oxygen species and increased susceptibility to bacterial and fungal infections, along with granuloma formation. CGD due to NCF2 mutations is less common than CYBB (gp91phox)–related CGD but is well documented and clinically significant.

In summary, p67phox is a crucial regulatory component of the phagocyte NADPH oxidase complex, coordinating cytosolic assembly, Rac signaling, and the oxidative burst essential for microbial killing.